TY - JOUR
T1 - The function of mitochondria in presynaptic development at the neuromuscular junction
AU - Lee, Chi Wai
AU - Peng, H. Benjamin
N1 - We are very grateful for helpful comments from anonymous reviewers in improving the article. This work was supported by Research Grants Council Grants HKUST6107/01M and AoE/B-15/01 and by National Institutes of Health Grant NS36754. C.W.L. is supported by the Croucher Foundation Fellowship.
PY - 2008/1
Y1 - 2008/1
N2 - Mitochondria with high membrane potential (ΔΨm) are enriched in the presynaptic nerve terminal at vertebrate neuromuscular junctions, but the exact function of these localized synaptic mitochondria remains unclear. Here, we investigated the correlation between mitochondrial ΔΨm and the development of synaptic specializations. Using mitochondrial ΔΨm-sensitive probe JC-1, we found that ΔΨm in Xenopus spinal neurons could be reversibly elevated by creatine and suppressed by FCCP. Along naïve neurites, preexisting synaptic vesicle (SV) clusters were positively correlated with mitochondrial ΔΨm, suggesting a potential regulatory role of mitochondrial activity in synaptogenesis. Indicating a specific role of mitochondrial activity in presynaptic development, mitochondrial ATP synthase inhibitor oligomycin, but not mitochondrial Na+/Ca2+ exchanger inhibitor CGP-37157, inhibited the clustering of SVs induced by growth factor–coated beads. Local F-actin assembly induced along spinal neurites by beads was suppressed by FCCP or oligomycin. Our results suggest that a key role of presynaptic mitochondria is to provide ATP for the assembly of actin cytoskeleton involved in the assembly of the presynaptic specialization including the clustering of SVs and mitochondria themselves.
AB - Mitochondria with high membrane potential (ΔΨm) are enriched in the presynaptic nerve terminal at vertebrate neuromuscular junctions, but the exact function of these localized synaptic mitochondria remains unclear. Here, we investigated the correlation between mitochondrial ΔΨm and the development of synaptic specializations. Using mitochondrial ΔΨm-sensitive probe JC-1, we found that ΔΨm in Xenopus spinal neurons could be reversibly elevated by creatine and suppressed by FCCP. Along naïve neurites, preexisting synaptic vesicle (SV) clusters were positively correlated with mitochondrial ΔΨm, suggesting a potential regulatory role of mitochondrial activity in synaptogenesis. Indicating a specific role of mitochondrial activity in presynaptic development, mitochondrial ATP synthase inhibitor oligomycin, but not mitochondrial Na+/Ca2+ exchanger inhibitor CGP-37157, inhibited the clustering of SVs induced by growth factor–coated beads. Local F-actin assembly induced along spinal neurites by beads was suppressed by FCCP or oligomycin. Our results suggest that a key role of presynaptic mitochondria is to provide ATP for the assembly of actin cytoskeleton involved in the assembly of the presynaptic specialization including the clustering of SVs and mitochondria themselves.
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-38749103445&origin=inward
U2 - 10.1091/mbc.e07-05-0515
DO - 10.1091/mbc.e07-05-0515
M3 - Journal article
SN - 1059-1524
VL - 19
SP - 150
EP - 158
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 1
ER -